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Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer's disease
- Source :
- Translational Neurodegeneration, Dipòsit Digital de Documents de la UAB, Universitat Autònoma de Barcelona, Translational Neurodegeneration, Vol 10, Iss 1, Pp 1-15 (2021), Dipòsit Digital de la UB, Universidad de Barcelona
- Publication Year :
- 2021
-
Abstract
- Background New fluid biomarkers for Alzheimer's disease (AD) that reveal synaptic and neural network dysfunctions are needed for clinical practice and therapeutic trial design. Dense core vesicle (DCV) cargos are promising cerebrospinal fluid (CSF) indicators of synaptic failure in AD patients. However, their value as biomarkers has not yet been determined. Methods Immunoassays were performed to analyze the secretory proteins prohormone convertases PC1/3 and PC2, carboxypeptidase E (CPE), secretogranins SgIII and SgII, and Cystatin C in the cerebral cortex (n = 45, provided by Bellvitge University Hospital) and CSF samples (n = 66, provided by The Sant Pau Initiative on Neurodegeneration cohort) from AD patients (n = 56) and age-matched controls (n = 55). Results In AD tissues, most DCV proteins were aberrantly accumulated in dystrophic neurites and activated astrocytes, whereas PC1/3, PC2 and CPE were also specifically accumulated in hippocampal granulovacuolar degeneration bodies. AD individuals displayed an overall decline of secretory proteins in the CSF. Interestingly, in AD patients, the CSF levels of prohormone convertases strongly correlated inversely with those of neurodegeneration markers and directly with cognitive impairment status. Conclusions These results demonstrate marked alterations of neuronal-specific prohormone convertases in CSF and cortical tissues of AD patients. The neuronal DCV cargos are biomarker candidates for synaptic dysfunction and neurodegeneration in AD.
- Subjects :
- medicine.medical_specialty
Cognitive Neuroscience
Tau protein
Cellular and Molecular Neuroscience
Cerebrospinal fluid
Alzheimer Disease
Internal medicine
medicine
Humans
Cognitive Dysfunction
Granulovacuolar degeneration
RC346-429
Cerebral Cortex
biology
business.industry
Research
Biochemical markers
Neurodegeneration
PCSK1
Alzheimer's disease
Cerebral cortex
PCSK2
medicine.disease
Dense Core Vesicles
Malaltia d'Alzheimer
Endocrinology
Secretory protein
medicine.anatomical_structure
Cystatin C
Carboxypeptidase E
Marcadors bioquímics
biology.protein
Biomarker (medicine)
Neurology (clinical)
Neurology. Diseases of the nervous system
business
Alzheimer’s disease
Biomarkers
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Translational Neurodegeneration, Dipòsit Digital de Documents de la UAB, Universitat Autònoma de Barcelona, Translational Neurodegeneration, Vol 10, Iss 1, Pp 1-15 (2021), Dipòsit Digital de la UB, Universidad de Barcelona
- Accession number :
- edsair.doi.dedup.....f5043526493941573da13f9651ce395e